DESCRIPTION: This subproject is designed to evaluate the defense mechanisms in the lung that protect against aspirated gastric contents. The study will evaluate how the acid is neutralized by analyzing how the cystic fibrosis transmembrane conductance regulator (CRTCR) and other anionic and non-anionic epithelial transport processes are involved. The second major objective of this subproject is concerned with how the hypo-osmotic aspirate is reabsorbed from the airways, specifically, in regard to aquaporins in the epithelial and endothelial membranes. To evaluate these specific aims, a careful review of the airway transport processes was done and the preliminary studies presented in this application relative to the specific aims are very impressive. The studies on the transport processes responsible for neutralization will be conducted using perfused rat lungs and isolated human derived tracheobronchial and bronchiole epithelial cells and primary isolated rat epithelial cells. The questions posed are: Is buffering by anion transport specific, does neutralization occur by OH transport, is cystic fibrosis transmembrane conductance regulator (CFTR) involved, can acceleration of neutralization of the airway fluid be stimulated by increasing anion transport, does amelioride affect acid neutralization, is carbonic anhydrase involved in this process, what are the effects of the epithelial transport systems and aquaporins on edema fluid removal and finally, what occurs with alkaline solution?